Together, these data support an important role for TMEM63C in maintaining ER-mitochondrialorganelle homeostasis and structure, likely to underlie HSP pathological outcomes.Maintained MERCs integrity is known to be of critical importance for a number of subcellularprocesses crucial for neuronal health, including lipid and calcium homeostasis.58 Our data show thatTMEM63C silencing alters organelle integrity of both mitochondria and ER,reflecting a potential role for this protein in the maintenance of these structures. Here, TMEM63C is linked to hereditary spastic paraplegia.