TMEM63C and hereditary spastic paraplegia: Indeed, multiple ER-shapingproteins have been involved in HSP and the loss of HSP-associated molecules leads to theexpansion of ER sheets at the cell periphery.36 Interestingly, silencing of TMEM63C in HeLa cellsdisrupted the balance between sheets and tubules by increasing ER-sheet area (Fig. 3A and B), suggesting that ER defects maycomprise a key pathomolecular aspect of TMEM63C-associated neurological disease.