CEP162: A critical regulator of ciliary transition zone assembly and its implications in ciliopathies

Abstract

CEP162, a 162-kDa centrosome protein, is a crucial centrosomal adapter, mediating cell differentiation and polarization. CEP162 maintains mitosis by dynamically stabilizing microtubules. CEP162 promotes the transition zone (TZ) assembly in the basal body through interaction with CEP131, CEP290, and axoneme microtubules as well as the distal centriole. TZ ensures the normal distribution of soluble proteins between the cytoplasm and cilia. It also facilitates retinal development and sperm flagellar motility. However, fluctuations in TZ permeability caused by abnormal expression of CEP162, including truncated mutations and naturally occurring mutations, lead to cilia abnormality and dysfunction in ciliogenesis through the regulation of intraflagellar transport, resulting in retinal degeneration and infertility. LncRNAs can induce SNP events in the CEP162 transcript by altering alternative splicing. Naturally occurring mutations are closely linked to retinal ciliopathy and diabetic retinopathy. This review summarizes the latest research progress to better understand the biology and pathophysiology of CEP162 and the clinical manifestations caused by CEP162 variants.