NEK8 is a serine/threonine kinase essential for renal tubular integrity and ciliary function 1. It localizes to cilia as part of the INV complex alongside inversin, ANKS6, and NPHP3, where it regulates ciliary protein trafficking and biogenesis 21. NEK8 plays critical roles in left-right determination and organ development, including kidney, heart, and liver 1, and regulates Hippo signaling pathway components 3. Biallelic NEK8 mutations cause syndromic ciliopathies including nephronophthisis-9 and renal-hepatic-pancreatic dysplasia-2 1. Recently, heterozygous missense variants in the kinase domain (p.Arg45Trp, p.Lys157Gln) were identified as a novel autosomal dominant cause of polycystic kidney disease, exhibiting dominant-negative effects 2. These variants impair polycystin-2 ciliary localization and reduce kinase activity, triggering increased DNA damage signaling 2. Beyond renal disease, NEK8 contributes to gastric cancer progression through asparagine metabolism reprogramming and mTORC1 pathway activation 4, and appears in childhood cardiomyopathy genetics 3. However, NEK8 pathogenic variants show no ocular manifestations despite causing systemic ciliopathies 5. The precise kinase substrates and regulatory mechanisms remain incompletely understood 1.