The roles of IKKα in normal physiology and cancer

IkappaB kinase alpha (IKKα) is a multifunctional serine/threonine kinase and a core component of the IKK complex, best known for its central role in canonical and non-canonical nuclear factor kappaB (NF-κB) signalling. While early studies primarily focused on these roles in NF-κB signalling, emerging evidence highlights a much broader spectrum of functions, extending far beyond these classical roles. IKKα is now known to govern diverse biological processes, including cell cycle regulation, epidermal differentiation, tissue homeostasis and development through NF-κB-independent mechanisms, acting as a transcriptional and epigenetic regulator and signalling mediator. In cancer, IKKα has dual, context-specific activities, both as a tumour suppressor through inhibition of cell growth in some settings, while also working as a potent oncogene driving cell proliferation, metastasis and therapy resistance in other settings. This review synthesises the current knowledge of IKKα in both physiological and pathological contexts, highlighting its multifaceted roles in cancer development and discussing emerging therapies targeting IKKα for cancer treatment.