KCTD1‐21 form a subgroup of BTB domain‐containing proteins that commonly function as Cullin3‐dependent E3 ligases.10 For example, KCTD5 is observed to act as a Cullin3 dependent off‐switch for GPCR signaling through ubiquitin‐mediated degradation of Gβγ under certain conditions.11 Similarly, KCTD6, KCTD11, and KCTD21 have been observed to ubiquitylate HDAC1 in complex with Cullin3, thereby suppressing Hedgehog activity in Medulloblastoma.12 KCTD8, KCTD12, and KCTD16 lack Cullin3 binding and instead act as auxiliary subunits of the GABAB2 receptors13 that help to modulate signaling outcomes.14 The gene discussed is KCTD12; the disease is medulloblastoma.