Pleckstrin homology domain-containing family M member 2 (PLEKHM2)

Pleckstrin homology domain-containing family M member 2 (PLEKHM2), also known as SKIP, is an adaptor protein containing pleckstrin homology (PH) and RUN domains that mediates the anterograde movement of lysosomes by linking them to kinesin-1 motor proteins via the lysosomal GTPase ARL8[1][3][4]. PLEKHM2 is essential for proper organelle positioning, lysosomal homeostasis, and autophagic flux. Mutations disrupting PLEKHM2 function cause abnormal lysosomal distribution, impaired autophagy, and are linked to rare inherited forms of dilated cardiomyopathy with left ventricular non-compaction[1][3][4]. PLEKHM2 also contributes to neuronal maturation, immune cell granule polarization, and resistance to certain infections, and is expressed in the cytoplasm and nuclei of most tissues, with highest levels in brain and testis[1][2][3][4]. Despite its central cellular roles, PLEKHM2 is not considered a traditional drug target (e.g., receptor, enzyme, or transporter), and no therapeutic drugs are currently known to selectively modulate its activity[1][3][4].

Other names

KIAA0842SKIPSifA and kinesin-interacting proteinSalmonella-induced filaments A and kinesin-interacting proteinPH domain-containing family M member 2Pleckstrin homology and RUN domain containing M2Novel RUN and PH domain-containing protein

Not established for drugs, as PLEKHM2 is not currently a direct drug target