In spinocerebellar ataxia type 11, truncated TTBK2 variants act as dominant‐negative mutants that impair ciliary stability and disrupt Sonic Hedgehog signaling.[27] Conversely, in medulloblastoma, TTBK2 maintains cilia‐dependent proliferative signaling through mechanisms that evade HUWE1‐mediated degradation.[122] Additional complexity arises from multi‐layered PTM networks, as exemplified by the macrophage migration inhibitory factor (MIF)‐phosphatidylinositol‐5‐phosphate 4‐kinase type 2 alpha (PIP4K2α)‐TTBK2 axis. This evidence concerns the gene HUWE1 and medulloblastoma.