Pleckstrin homology domain-containing family A member 4 (PLEKHA4)

Pleckstrin homology domain-containing family A member 4 (PLEKHA4) is a plasma membrane-associated adaptor protein characterized by an N-terminal pleckstrin homology (PH) domain, which mediates specific binding to phosphoinositides such as PI(4,5)P2 and/or PtdIns3P[1][3]. PLEKHA4 assembles into higher-order structures at PI(4,5)P2-enriched regions of the plasma membrane and recruits the E3 ubiquitin ligase adaptor KLHL12, attenuating CUL3-KLHL12-mediated polyubiquitination of Dishevelled (DVL)[1]. This regulation modulates both canonical (β-catenin dependent) and non-canonical (planar cell polarity) Wnt signaling by setting DVL protein levels and membrane localization[1]. Elevated PLEKHA4 expression is observed in some melanomas[2][3], implicating potential roles in oncogenic signaling, though it is not a validated therapeutic target, nor are there known direct drug interactions. It has no known role as a classical receptor, enzyme, or transporter, but functions as a phosphoinositide-binding adaptor protein involved in membrane signaling organization and the spatial regulation of ubiquitination machinery[1][3].

Other names

PEPP1PEPP-1Phosphoinositol 3-phosphate-binding protein 1Phosphoinositol 3-phosphate-binding PH domain protein 1Pleckstrin homology domain-containing family A member 4PH domain-containing family A member 4Pleckstrin homology domain-containing, family A (phosphoinositide binding specific) member 4