FAM134B in Cellular Homeostasis: Bridging Endoplasmic Reticulum-Phagy to Human Diseases.

FAM134B, originally characterized as an oncogene in esophageal squamous carcinoma, has also been implicated in the pathogenesis of hereditary sensory and autonomic neuropathy type IIB (HSAN2B). It is recognized as the inaugural endoplasmic reticulum (ER)-phagy receptor in mammals containing an LC3-interacting region, which facilitates its interaction with LC3 and GABARAP proteins in the autophagosome. ER-phagy, a critical process involved in ER quality control, selectively degrades superfluous or damaged ER fragments in lysosomes, thereby maintaining ER and protein homeostasis. This review offers an in-depth analysis of FAM134B's structure, function, and regulation, emphasizing its role in infectious diseases, neuropathies, cancer, metabolic disorders, degenerative conditions, and cardiovascular diseases. The evidence presented highlights the need for further research on FAM134B as a potential therapeutic target in human diseases.