Alternative splicing is a key regulatory mechanism that significantly contributes to the generation of protein diversity from a limited number of genes. It plays a crucial role in tissue and organ development, as well as in maintaining tissue homeostasis. Alternative splicing generates multiple transcript and protein isoforms from a single gene, and its coordination is essential for proper development. Recent studies have shown that alternative splicing is involved in various developmental processes and that its dysregulation can lead to diseases. Alternative splicing is regulated by a variety of factors, including cis-regulatory sequences in pre-mRNAs and trans-acting factors such as RNA-binding proteins (RBPs) and splicing factors. These factors influence the inclusion or exclusion of specific exons, leading to the generation of different protein isoforms. The regulation of alternative splicing is complex and involves multiple layers, including the expression levels, localization, and splicing of RBPs. Additionally, splicing can occur co-transcriptionally, allowing for a mechanistic interplay between the transcriptional and splicing machineries. In the brain, alternative splicing is crucial for neuronal differentiation and development. RBPs such as PTBP1, PTBP2, and RBFOX1 regulate splicing events that are essential for proper development. For example, PTBP1 and PTBP2 engage in a cross-talk that affects the inclusion or exclusion of specific exons, influencing neuronal development. Similarly, RBFOX1 regulates alternative splicing events that are important for neuronal differentiation and synaptic function. In cardiac muscle, alternative splicing is essential for the regulation of mechanical properties and the development of the heart. The splicing of the titin gene, which is involved in the structure and elasticity of cardiac muscle, is regulated by RBM20. Mutations in RBM20 can lead to dilated cardiomyopathies. Additionally, alternative splicing of the M-line associated portion of titin is regulated by splicing factors and can have tissue-specific functions. In skeletal muscle, alternative splicing is important for muscle development and function. The splicing of genes involved in ion transport, structural functions, excitation-contraction coupling, and metabolism is regulated by RBPs such as MEF2D and ROCK2. Misregulation of alternative splicing can lead to diseases such as myotonic dystrophy, where the mis-splicing of specific exons results in the expression of fetal protein isoforms in adult tissues. In other tissues and organs, alternative splicing plays a role in development and physiology. For example, in the pancreas, alternative splicing is regulated by inflammatory cytokines and fatty acids, and can affect exocytosis, apoptosis, insulin signaling, and transcription regulation. In the liver, alternative splicing is involved in the development and maturation of hepatocytes, and the regulation of splicing factors such as SRSF3 and SRSF10 is important for liver homeostasis and metabolism. InAlternative splicing is a key regulatory mechanism that significantly contributes to the generation of protein diversity from a limited number of genes. It plays a crucial role in tissue and organ development, as well as in maintaining tissue homeostasis. Alternative splicing generates multiple transcript and protein isoforms from a single gene, and its coordination is essential for proper development. Recent studies have shown that alternative splicing is involved in various developmental processes and that its dysregulation can lead to diseases. Alternative splicing is regulated by a variety of factors, including cis-regulatory sequences in pre-mRNAs and trans-acting factors such as RNA-binding proteins (RBPs) and splicing factors. These factors influence the inclusion or exclusion of specific exons, leading to the generation of different protein isoforms. The regulation of alternative splicing is complex and involves multiple layers, including the expression levels, localization, and splicing of RBPs. Additionally, splicing can occur co-transcriptionally, allowing for a mechanistic interplay between the transcriptional and splicing machineries. In the brain, alternative splicing is crucial for neuronal differentiation and development. RBPs such as PTBP1, PTBP2, and RBFOX1 regulate splicing events that are essential for proper development. For example, PTBP1 and PTBP2 engage in a cross-talk that affects the inclusion or exclusion of specific exons, influencing neuronal development. Similarly, RBFOX1 regulates alternative splicing events that are important for neuronal differentiation and synaptic function. In cardiac muscle, alternative splicing is essential for the regulation of mechanical properties and the development of the heart. The splicing of the titin gene, which is involved in the structure and elasticity of cardiac muscle, is regulated by RBM20. Mutations in RBM20 can lead to dilated cardiomyopathies. Additionally, alternative splicing of the M-line associated portion of titin is regulated by splicing factors and can have tissue-specific functions. In skeletal muscle, alternative splicing is important for muscle development and function. The splicing of genes involved in ion transport, structural functions, excitation-contraction coupling, and metabolism is regulated by RBPs such as MEF2D and ROCK2. Misregulation of alternative splicing can lead to diseases such as myotonic dystrophy, where the mis-splicing of specific exons results in the expression of fetal protein isoforms in adult tissues. In other tissues and organs, alternative splicing plays a role in development and physiology. For example, in the pancreas, alternative splicing is regulated by inflammatory cytokines and fatty acids, and can affect exocytosis, apoptosis, insulin signaling, and transcription regulation. In the liver, alternative splicing is involved in the development and maturation of hepatocytes, and the regulation of splicing factors such as SRSF3 and SRSF10 is important for liver homeostasis and metabolism. In