The endoplasmic reticulum (ER) is a complex environment where proteins are folded and modified. ER quality control (ERQC) ensures that only properly folded proteins are allowed to proceed to their final destinations, while misfolded or unassembled proteins are degraded via the ER-associated degradation (ERAD) pathway. ERAD involves molecular chaperones and factors that recognize and target substrates for retrotranslocation to the cytoplasm, where they are degraded by the ubiquitin–proteasome system. ERAD is crucial for preventing protein misfolding-induced toxicity and is involved in various diseases. The ERAD pathway includes several steps: substrate recognition, targeting, retrotranslocation, ubiquitylation, and proteasomal degradation. ERAD is regulated and interacts with other pathways such as autophagy and the unfolded protein response (UPR), which can lead to apoptosis if unmitigated. ERAD also plays a role in protein transport to later compartments of the secretory pathway. The ERAD pathway has been studied extensively, and recent findings highlight its importance in maintaining cellular homeostasis and preventing disease. Key components of ERAD include molecular chaperones, ubiquitin ligases, and proteasomes. ERAD is essential for the degradation of misfolded proteins and is involved in various cellular processes, including the degradation of disease-related proteins. The ERAD pathway is complex and involves multiple steps, with different factors and enzymes playing specific roles in each step. Understanding ERAD is important for developing therapies for diseases associated with protein misfolding.The endoplasmic reticulum (ER) is a complex environment where proteins are folded and modified. ER quality control (ERQC) ensures that only properly folded proteins are allowed to proceed to their final destinations, while misfolded or unassembled proteins are degraded via the ER-associated degradation (ERAD) pathway. ERAD involves molecular chaperones and factors that recognize and target substrates for retrotranslocation to the cytoplasm, where they are degraded by the ubiquitin–proteasome system. ERAD is crucial for preventing protein misfolding-induced toxicity and is involved in various diseases. The ERAD pathway includes several steps: substrate recognition, targeting, retrotranslocation, ubiquitylation, and proteasomal degradation. ERAD is regulated and interacts with other pathways such as autophagy and the unfolded protein response (UPR), which can lead to apoptosis if unmitigated. ERAD also plays a role in protein transport to later compartments of the secretory pathway. The ERAD pathway has been studied extensively, and recent findings highlight its importance in maintaining cellular homeostasis and preventing disease. Key components of ERAD include molecular chaperones, ubiquitin ligases, and proteasomes. ERAD is essential for the degradation of misfolded proteins and is involved in various cellular processes, including the degradation of disease-related proteins. The ERAD pathway is complex and involves multiple steps, with different factors and enzymes playing specific roles in each step. Understanding ERAD is important for developing therapies for diseases associated with protein misfolding.