The emerging link between IP(3) receptor turnover and Hereditary Spastic Paraplegia

IP(3) receptor turnover is mediated by the ubiquitin ligase RNF170, which is recruited to active IP(3) receptors by the erlin1/2 complex. A new study by Wagner et al (Nat Commun, 2019) links four cases of Hereditary Spastic Paraplegia to inactivating mutations in RNF170. This increases the number of examples of mutations to the erlin1/2 complex-RNF170 module underlying neurodegenerative disorders.