ERLIN1

ERLIN1 (SPFH1, ER lipid raft-associated protein 1) is a single-pass type II endoplasmic reticulum (ER) membrane protein with a lumenal SPFH/prohibitin (band 7) domain, belonging to the band 7/mec-2 (stomatin-prohibitin-flotillin) family. It associates with lipid-raft-like domains of the ER membrane and functions as a scaffold rather than an enzyme. ERLIN1 forms a large ring-shaped heteromeric complex with its homolog ERLIN2 (SPFH2); the ERLIN1/ERLIN2 complex binds inositol 1,4,5-trisphosphate receptor (IP3R) tetramers and, together with the ER ubiquitin ligase RNF170, mediates the ER-associated degradation (ERAD) of activated IP3Rs, thereby controlling calcium signaling. The erlins are cholesterol-binding proteins that restrict SREBP activation: they associate with the SCAP-SREBP-Insig machinery to promote its ER retention and thus negatively regulate cholesterol and fatty acid biosynthesis, contributing to cellular cholesterol homeostasis. ERLIN1 also interacts with the ER ubiquitin ligases AMFR/gp78 and SYVN1/HRD1, linking it to sterol-accelerated ERAD. Loss-of-function variants in ERLIN1 cause autosomal recessive hereditary spastic paraplegia (SPG62).

Disorders

Relationship is the entry's genetic[].relationship_type. untyped means the entry has a genetic record for the gene but does not type it; its free-text association is shown instead.

An entry matches when ClinGen's MONDO disease is the entry's own disease term, a subtype term, or an exact-match mapping. An amber status marks an entry ClinGen supports the gene for (Definitive, Strong or Moderate) whose own record does not type it. A Limited, Disputed or Refuted tier on such an entry is not a gap.

• corticospinal_tract_axonopathy via Hereditary Spastic Paraplegia