Nuclear factor kappa-B inhibitor alpha (IκBα (also NFKBIA))

Nuclear factor kappa-B inhibitor alpha (IκBα, encoded by NFKBIA) is a key regulatory protein that inhibits the nuclear factor kappa-light-chain-enhancer of activated B cells (NF‑κΒ) transcription factors. It functions by binding to NF‑kΒ complexes in the cytoplasm, masking their nuclear localization signals, thereby preventing their translocation into the nucleus where they would activate genes involved in immunity, inflammation, cell survival, and development. Upon receiving specific cellular signals—such as those from cytokines or stress—the upstream kinase complex phosphorylates IΚΒα leading to its ubiquitination and subsequent degradation via the proteasome system. This releases active NF‑kΒ dimers which then enter the nucleus to regulate gene expression critical for immune responses and other cellular processes. Mutations or dysregulation in NFKΒΙΑ are implicated in immunodeficiency syndromes such as anhidrotic ectodermal dysplasia with immune deficiency as well as certain cancers like Hodgkin’s lymphoma due to constitutive activation of NF-kΒ signaling pathways[1][2].

Other names

IκBαNFKBIANF-kappa-B inhibitor alphaNuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor alpha

Drugs targeting this molecule or its pathway typically act by stabilizing IκBα to prevent its degradation, thereby keeping NF‑κB sequestered in the cytoplasm and inhibiting its transcriptional activity. Some agents may also inhibit upstream kinases that phosphorylate IκBs.