The article reviews the structure and function of sphingolipid- and cholesterol-rich membrane rafts, which are specialized lipid domains found in cellular membranes. These rafts are characterized by tightly packed sphingolipids and high cholesterol content, leading to phase separation from the disordered state (Lα, Ls, or Ld) of phospholipids. The presence of rafts is supported by detergent-insoluble membranes (DRMs) isolated from cells, which are rich in cholesterol and sphingolipids and exhibit the Ls phase. The formation of rafts is influenced by the differential packing ability of sphingolipids and phospholipids, as well as the presence of cholesterol, which can promote phase separation. Rafts are crucial for signaling in hematopoietic cells, particularly in T cells and basophils. Antigen binding to receptors on these cells triggers receptor cross-linking, leading to the activation of Src family tyrosine kinases and subsequent signaling cascades. Clustering of receptors, such as the T cell receptor (TCR) and FcεR, can induce raft formation and enhance signaling. Mutagenesis studies have shown that proteins like Lck and LAT must be in rafts to function effectively. Additionally, cholesterol depletion disrupts raft function, affecting signaling and other cellular processes. The article also discusses the distribution of rafts in different cellular compartments, their coupling between the inner and outer leaflets of the bilayer, and their potential roles in other cellular processes such as sorting in the trans-Golgi network and endocytic pathway. Overall, the review highlights the importance of rafts in cellular signaling and their complex dynamics and interactions with other cellular components.The article reviews the structure and function of sphingolipid- and cholesterol-rich membrane rafts, which are specialized lipid domains found in cellular membranes. These rafts are characterized by tightly packed sphingolipids and high cholesterol content, leading to phase separation from the disordered state (Lα, Ls, or Ld) of phospholipids. The presence of rafts is supported by detergent-insoluble membranes (DRMs) isolated from cells, which are rich in cholesterol and sphingolipids and exhibit the Ls phase. The formation of rafts is influenced by the differential packing ability of sphingolipids and phospholipids, as well as the presence of cholesterol, which can promote phase separation. Rafts are crucial for signaling in hematopoietic cells, particularly in T cells and basophils. Antigen binding to receptors on these cells triggers receptor cross-linking, leading to the activation of Src family tyrosine kinases and subsequent signaling cascades. Clustering of receptors, such as the T cell receptor (TCR) and FcεR, can induce raft formation and enhance signaling. Mutagenesis studies have shown that proteins like Lck and LAT must be in rafts to function effectively. Additionally, cholesterol depletion disrupts raft function, affecting signaling and other cellular processes. The article also discusses the distribution of rafts in different cellular compartments, their coupling between the inner and outer leaflets of the bilayer, and their potential roles in other cellular processes such as sorting in the trans-Golgi network and endocytic pathway. Overall, the review highlights the importance of rafts in cellular signaling and their complex dynamics and interactions with other cellular components.