SHH and holoprosencephaly: GLI2 acts as an effector of Sonic hedgehog signaling (Shh), a pathway that was previously observed to be activated in human and murine tissues of ADPKD and non-ADPKD cystic kidney disease.17 While loss-of-function of GLI2 is associated with hypopituitarism and holoprosencephaly (MIM 615849/610829) it was also found to alleviate cystic kidney disease in a murine PKD model, suggesting that gain of function may exert an opposite effect.18 ID20.1 reported a negative family history and presented with bilateral PKD without liver cysts and ESRD at the age of 64.