ER-transmembrane protein Niemann-Pick type C (NP1) is degraded in a FAM134B dependent manner, and recently phosphatidylinositol-3-phosphate (PI3P)-binding protein TOLLIP has been identified to promote degradation of mutated ER transmembrane proteins including spastic paraplegia-associated Seipin and an amyotrophic lateral sclerosis (ALS)-linked mutant of VAPB (Hayashi et al., 2023). This evidence concerns the gene RETREG1 and amyotrophic lateral sclerosis.