NCKAP5L (also known as Cep169) is a centrosomal protein that regulates microtubule organization and stability through multiple mechanisms. The protein functions as a microtubule plus-end tracking protein (+TIP) that directly binds microtubules via its C-terminal domain and forms homodimers through its N-terminal domain, both of which are required for its biological activity 1. NCKAP5L stabilizes microtubules by promoting their acetylation and facilitates bundling and crosslinking of adjacent microtubules 12. The protein interacts with CDK5RAP2 at centrosomes and EB1 at microtubule plus-ends, positioning it as a key regulator of microtubule dynamics 2. During mitosis, Cdk1-mediated phosphorylation of NCKAP5L at consensus sites triggers its dissociation from centrosomes, potentially regulating mitotic spindle dynamics 3. Clinically, NCKAP5L demonstrates significant disease relevance. The gene is upregulated across multiple cancer types and serves as a promising biomarker for cancer diagnosis and prognosis, particularly colorectal cancer, with high expression correlating with patient survival and immune cell infiltration 4. Additionally, homozygous recessive mutations in NCKAP5L have been identified in autism cases, suggesting a role in neuronal function 5. NCKAP5L also appears as a candidate gene for cold climate adaptation in domestic mammals through cytoskeleton-related pathways 6.