Karyopherin subunit alpha-2 (KPNA2)

Karyopherin subunit alpha-2 (KPNA2) is a nuclear transport adaptor protein of the karyopherin alpha family, also known as importin subunit alpha-1[5]. It mediates nucleocytoplasmic trafficking by recognizing and binding to nuclear localization signals (NLS) on cargo proteins—such as transcription factors, DNA damage response proteins (BRCA1, Chk2, NBS1), and others—and facilitating their import into the nucleus in conjunction with importin beta[1][2][3]. KPNA2 also plays a role in exporting certain response molecules. Dysregulation and overexpression of KPNA2 have been identified as a hallmark of multiple cancers, where elevated KPNA2 levels are associated with aggressive tumor features, increased cell proliferation, poor prognosis, and therapy resistance[1][3][4][5]. KPNA2 modulates pathways central to cancer biology, including STAT3-mediated PD-L1 upregulation (immune escape) and cancer stem cell maintenance. Its high expression makes it a biomarker for cancer prognosis and potentially a novel therapeutic target, though direct inhibitors are not clinically available, and systemic safety concerns remain significant[2][3][4].

Other names

Importin subunit alpha-1Importin alpha 1RCH1SRP1SRP1alphaIPOA1QIP2PTAC58RAG cohort protein 1SRP1-alphaimportin-alpha-P1pendulin

Inhibition of KPNA2 may reduce nuclear import of oncogenic or DNA repair factors[3][4]. Modulation of immune checkpoint regulation via inhibition of STAT3/PD-L1 nuclear translocation[2]. Potential effects on tumor cell viability, migration, stemness, or therapy resistance[4].