Tissue-specific targeting has allowed further insight into the physiological roles of VPS34, with loss of VPS34 leading to cardiomyopathy and cardiomegaly in the heart [139, 140], hepatomegaly and hepatic steatosis in the liver [139], rod cell degeneration in the retina [141], neurodegeneration in the nervous system [142–144], and defective T cell survival and homeostasis [145, 146]. Here, PIK3C3 is linked to cardiomyopathy.