ERLIN1 encodes an endoplasmic reticulum (ER)-resident protein that forms oligomeric ring-like complexes with ERLIN2, creating specialized membrane nanodomains critical for multiple cellular processes 1. The primary function involves protein quality control through the ER-associated degradation (ERAD) pathway, where ERLIN1/2 complexes scaffold interactions between TMUB1 and RNF170 to facilitate degradation of misfolded proteins 1. ERLIN1 also regulates lipid homeostasis by restricting cholesterol esterification and promoting cholesterol transport from ER to Golgi, thereby affecting secretory pathway function 1. Additionally, ERLIN1 maintains autophagy by directly binding and stabilizing phosphatidylinositol 3-phosphate (PI(3)P), with complex disruption reducing cellular PI(3)P levels by ~50% and decreasing autophagic flux 2. Disease relevance includes mutations causing spastic paraplegia 62 (SPG62), a rare hereditary spastic paraplegia subtype, as demonstrated by a novel splicing mutation disrupting the conserved prohibitin domain 3. Clinically, the common p.Ile291Val variant shows protective effects against metabolic dysfunction-associated steatotic liver disease (MASLD), functioning as a potential gain-of-function mutation that reduces liver enzyme levels while increasing plasma lipid levels 4. ERLIN1 variants also influence fatty liver disease susceptibility and hepatic inflammation 5.