AHNAK nucleoprotein 2 (AHNAK2)

AHNAK nucleoprotein 2 (AHNAK2) is a giant protein (>600 kDa), composed of a PDZ domain-containing short N-terminal, a central domain of 24 repetitive β-propeller-like units, and a large C-terminal segment[1][3][5]. It is expressed in several tissues, particularly in epithelia, smooth muscle, brain, and the periphery[4]. AHNAK2 is involved in cell adhesion, cytoskeletal organization, and especially in the regulation of L-type calcium channels, where it may act as a scaffold linking the cytoskeleton to the plasma membrane and modulating calcium signaling[1][3][5]. It is highly overexpressed in multiple cancers, where it promotes tumor progression, metastasis, and cell migration through activation of pathways such as PI3K, NF-κB, and Wnt/β-catenin[1][2][5]. In clinical settings, AHNAK2 is a recognized biomarker for several aggressive malignancies, but there are currently no approved drugs or known small molecules targeting this protein directly[2][5]. Recent studies note its additional role in non-classical protein secretion, such as FGF1 export under stress, and germline mutations in AHNAK2 are linked to certain hereditary neuropathies[5].

Other names

AHNAK2Protein AHNAK2C14orf78KIAA2019