Tubulin tyrosine ligase-like protein 12 (TTLL12)

Tubulin tyrosine ligase-like protein 12 (TTLL12) is the least characterized and most divergent member of the tubulin tyrosine ligase-like (TTLL) enzyme family, which mainly catalyzes post-translational modifications of tubulin[4][2]. Unlike other TTLL family members, TTLL12 acts as a pseudo-enzyme: it contains SET-like and TTL-like domains but exhibits no enzymatic activity as a ligase, glutamylase, or methyltransferase in standard assays[2][4]. Instead, TTLL12 indirectly regulates post-translational modifications on both tubulin (altering detyrosination, polyglutamylation, acetylation, methylation) and histone H4 methylation states, affecting cell division, chromosome stability, and ciliogenesis[3][7][4]. TTLL12 is implicated in several pathological and physiological contexts, including tumor progression (via modulation of tubulin modifications linked to cancer and metastasis), the innate immune response (by regulating interferon signaling pathways), and ciliogenesis (important for cellular structure and function)[3][7][2]. The novelty and indirect action of TTLL12—and the discovery of alternatively spliced isoforms—make it a molecule of interest for further research in both oncology and cell biology, although no drugs are currently known to act directly on TTLL12[4][2][3].

Other names

KIAA0153dJ526I14.2Inactive tubulin-tyrosine ligase-like protein 12tubulin tyrosine ligase-like family, member 12

Not directly targeted by any approved drug; mechanisms would likely involve modulation of tubulin post-translational modification pathways if targeted