Ankyrin repeat and LEM domain-containing protein 2 (ANKLE2)

Ankyrin repeat and LEM domain-containing protein 2 (ANKLE2) is a member of the LEM family of inner nuclear membrane proteins that plays a pivotal regulatory role in postmitotic nuclear envelope reassembly[2][4][5][6]. It does so primarily by coordinating the dephosphorylation of barrier-to-autointegration factor (BAF) through the recruitment of protein phosphatase 2A (PP2A) and inhibiting VRK1 kinase activity[1][3][4]. Its structure includes ankyrin repeats, a LEM (LAP2, Emerin, MAN1) domain, and a transmembrane region[3][4]. ANKLE2 anchors to the endoplasmic reticulum and nuclear envelope, and its loss disrupts nuclear morphology, BAF function, and proper cell division, leading to developmental brain defects such as microcephaly[3][4][6]. It can be targeted by viral proteins such as Zika virus NS4A, which phenocopies microcephaly seen in congenital Zika syndrome[3][4]. Altered expression and function of ANKLE2 may also be involved in cancer progression, given its role in cell cycle and nuclear envelope integrity[6]. No approved drugs are known to selectively target ANKLE2 at present.

Other names

LEM4KIAA0692LEMD7Lem4MCPH16