NEK1 (NIMA-related kinase 1) is a serine/threonine kinase with multiple cellular functions critical for neuronal health and development. The protein primarily functions in DNA damage checkpoint control and repair, phosphorylating VDAC1 in response to DNA damage to limit mitochondrial cell death 1. NEK1 is essential for cilium assembly and primary ciliary structure maintenance, with mutations causing ciliary abnormalities and impaired sonic hedgehog signaling 23. The kinase regulates metabolic pathways by phosphorylating malic enzyme 1 (ME1) at S336, counteracting acetylation-mediated activation and affecting NADPH production and lipogenesis 4. NEK1 variants are significantly associated with amyotrophic lateral sclerosis (ALS), representing one of seven novel ALS genes identified since 2014 5. Loss-of-function NEK1 mutations cause ALS through ciliary dysfunction, cell cycle re-entry, disrupted tubulin acetylation, and impaired DNA damage response 3. In ALS cohorts, NEK1 variants are found in approximately 2.6% of patients, with loss-of-function variants associated with shorter survival times and upper limb onset 67. The protein's dysfunction contributes to ALS pathogenesis through multiple mechanisms including mitochondrial alterations and calcium homeostasis disruption 3.