PLEKHM1

The protein encoded by this gene is essential for bone resorption, and may play a critical role in vesicular transport in the osteoclast. Mutations in this gene are associated with autosomal recessive osteopetrosis type 6 (OPTB6). Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq]

pleckstrin homology domain containing, family M (with RUN domain) member 1

Acts as a multivalent adapter protein that regulates Rab7-dependent and HOPS complex-dependent fusion events in the endolysosomal system and couples autophagic and the endocytic trafficking pathways. Acts as a dual effector of RAB7A and ARL8B that simultaneously binds these GTPases, bringing about clustering and fusion of late endosomes and lysosomes (PubMed:25498145, PubMed:28325809).
Required for late stages of endolysosomal maturation, facilitating both endocytosis-mediated degradation of growth factor receptors and autophagosome clearance. Interaction with Arl8b is a crucial factor in the terminal maturation of autophagosomes and to mediate autophagosome-lysosome fusion (PubMed:25498145).
Positively regulates lysosome peripheral distribution and ruffled border formation in osteoclasts (By similarity).
May be involved in negative regulation of endocytic transport from early endosome to late endosome/lysosome implicating its association with Rab7 (PubMed:20943950).
May have a role in sialyl-lex-mediated transduction of apoptotic signals (PubMed:12820725).
Involved in bone resorption (By similarity).
(Microbial infection) In case of infection contributes to Salmonella typhimurium pathogenesis by supporting the integrity of the Salmonella-containing vacuole (SCV) probably in concert with the HOPS complex and Rab7.

Autophagosome-lysosome fusionManual Assertion Based On ExperimentIMP:UniProtKB
Late endosome to lysosome transportManual Assertion Based On ExperimentIMP:UniProtKB
Lysosome localizationManual Assertion Based On ExperimentIDA:UniProtKB
Positive regulation of bone resorptionISS:UniProtKB
Positive regulation of ruffle assemblyISS:UniProtKB
Protein transportIEA:UniProtKB-KW

Autolysosome membrane
Endosome membrane
Late endosome membrane
Lysosome membrane
In case of infection colocalizes with Salmonella typhimurium sifA in proximity of Salmonella-containing vacuole (SCV) (PubMed:25500191).

Osteopetrosis, autosomal recessive 6 (OPTB6):
A rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and a benign autosomal dominant form occurring in adolescence or adulthood. Recessive osteopetrosis commonly manifests in early infancy with macrocephaly, feeding difficulties, evolving blindness and deafness, bone marrow failure, severe anemia, and hepatosplenomegaly. Deafness and blindness are generally thought to represent effects of pressure on nerves.
Osteopetrosis, autosomal dominant 3 (OPTA3):
A form of osteopetrosis, a rare genetic disease characterized by abnormally dense bone, due to defective resorption of immature bone. Osteopetrosis occurs in two forms: a severe autosomal recessive form occurring in utero, infancy, or childhood, and an autosomal dominant form occurring in adolescence or adulthood. OPTA3 is characterized by typical features of osteopetrosis such as fractures after minor trauma, early tooth loss, anemia, hepatosplenomegaly, and a generalized increase in bone mineral density. Some patients exhibit localized osteosclerosis and generalized osteopenia.