PLEKHM1 is a member of the M family of Pleckstrin homolog domain-containing proteins, a group of proteins containing a RUN domain, two pleckstrin homology domains, and a cysteine-rich domain. It was identified through segregation analysis as a cause of osteopetrosis in humans. PLEKHM1 co-localizes with Rab7 to late endosomal/lysosomal vesicles in HEK293 and osteoclast-like cells, with this co-localization dependent on the prenylation of Rab7. Monocytes from a patient homozygous for a mutated form of PLEKHM1differentiated into osteoclasts normally, but failed to form ruffled borders and showed little evidence of bone resorbtion when cultured on dentine discs. Another mutation of PLEKHM1 impaired vesicular acidification and increased TRACP secretion in osteoclasts, suggesting that PLEKHM1 has critical roles in endosomal maturation and may be important in osteoclast-osteoblast cross-talk.
162 kDa adapter protein; AP162; AP162, B2, OPTB6; PH domain-containing family M member 1; pleckstrin homology domain containing, family M (with RUN domain) member 1; Pleckstrin homology domain-containing family M member 1