TCTN2 is a transition zone protein essential for ciliary structure and hedgehog signaling. As a component of the tectonic-like complex at the ciliary transition zone, TCTN2 functions as a selective barrier regulating transmembrane protein diffusion between the cilium and plasma membrane 1. TCTN2 depletion causes partial transition zone damage, ciliary membrane protein loss, and intraflagellar transport protein leakage, resulting in cilium shortening and structural defects 1. The protein is critical for sonic hedgehog (Shh) pathway activation, particularly in prechordal plate development where reduced hedgehog signaling in TCTN2 mutants leads to increased neuronal cell death and facial midline collapse 2. TCTN2 mutations cause multiple ciliopathies: Meckel-Gruber syndrome (characterized by encephalocele, polycystic kidneys, and polydactyly) 3 and Joubert syndrome (characterized by cerebellar dysplasia and developmental delay) 4. Recent evidence suggests distinct functions for lncRNA TCTN2 in cancer biology and neuroprotection, where it regulates cell proliferation and autophagy through microRNA pathways 56. TCTN2's role in hedgehog signaling-dependent dorsal-ventral patterning can be therapeutically manipulated in neural tissue engineering 7. Understanding TCTN2 mechanisms is crucial for developing ciliopathy treatments.