Mechanistically, OCRL is a 5’-lipid phosphatase, and loss of OCRL elevates PI(4,5)P2 levels, which is consistent with findings in LS patient cells (Wenk et al, 2001; Akhtar et al, 2022) and in our OCRLKO model (Fig. 2, this study). The gene discussed is OCRL; the disease is Leigh syndrome.