Collectively, our data provide the pathomechanistic basis for the organ-specific abnormalities seen in patients with KCTD1 or KCTD15 mutations, identify KCTD1/KCTD15 complexes as critical regulators of ectodermal and NCC functions, and define membranous ACC as a neurocristopathy. The gene discussed is SLC12A3; the disease is adrenal cortex carcinoma.