These findings indicate that ER PC2 might not be causal to ADPKD, but rather a loss-of-function of PC2 at the primary cilium (that does not interact with TMEM33) is responsible for cystogenesis, as already indicated by the tight association between renal cystic diseases and numerous ciliopathies60. Here, PKD2 is linked to autosomal dominant polycystic kidney disease.