LisH domain-containing protein ARMC9

ARMC9 is a LisH domain-containing protein that plays a crucial role in ciliogenesis, particularly in regulating ciliary microtubule acetylation and polyglutamylation, and controlling cilium length (UniProt: Q7Z3E5). The protein also acts as a positive regulator of hedgehog signaling through its presumed involvement in trafficking and retention of GLI2 and GLI3 proteins at the ciliary tip. Mutations in ARMC9 cause Joubert syndrome 30 (JBTS30; MIM 617622), an autosomal recessive disorder characterized by cerebellar vermian hypoplasia, oculomotor apraxia, and psychomotor delay.

In Alzheimer's disease, ARMC9 is consistently downregulated in post-mortem AD brain tissue compared to age-matched controls (Chaparral AD proteomics, mean log2FC: −0.4286). This observation derives from TMT-labeled proteomics across four subcellular fractions. The downregulation suggests potential disruption of ciliary function or hedgehog signaling integrity in the AD brain, though the functional consequences of reduced ARMC9 levels in neurodegeneration remain to be clarified.