| TMEM55A — Transmembrane Protein 55A | |
|---|---|
| Symbol | TMEM55A |
| Current Symbol | PIP4P2 (Phosphatidylinositol-4,5-bisphosphate 4-phosphatase 2) |
| Full Name | Transmembrane protein 55A / Type 2 PtdIns-4,5-P2 4-phosphatase |
| Chromosome | 8q13.1 |
| NCBI Gene | 55529 |
| Ensembl | ENSG00000149547 |
| OMIM | 609864 |
| UniProt | Q8N4L2 |
| Protein | PIP4P2 (257 aa, Type II transmembrane lysosomal protein) |
| Diseases | [Parkinson's Disease](/diseases/parkinsons-disease) (therapeutic target) |
| Expression | [Brain](/brain-regions/brain), [Substantia Nigra](/brain-regions/substantia-nigra), lysosomal compartments |
| Key Aliases | |
| PIP4P2, PP4P2, TMEM55A, MDP1, NTP3 | |
TMEM55A (current official symbol: PIP4P2, also known as phosphatidylinositol-4,5-bisphosphate 4-phosphatase 2) is a gene on chromosome 8q13.1 encoding a 257-amino acid Type II transmembrane protein localized primarily to lysosomal membranes. Originally cloned and characterized in 2006,[@pubmed16365287] TMEM55A has emerged as a novel therapeutic target in Parkinson's disease based on recent multi-omics network analysis demonstrating its role in endolysosomal pathway dysfunction[@pubmed41866087].
TMEM55A is a transmembrane protein localized to endolysosomal membranes where it plays a critical role in regulating phosphatidylinositol (PI) signaling and lysosomal function.
TMEM55A/PIP4P2 is a Type II transmembrane protein with:
The protein catalyzes the hydrolysis of phosphatidylinositol-4,5-bisphosphate (PtdIns-4,5-P2) to phosphatidylinositol-4-phosphate (PtdIns-4-P), making it a key regulator of phosphoinositide signaling at the lysosomal membrane.
TMEM55A functions as a type 2 phosphatidylinositol-4,5-bisphosphate 4-phosphatase (EC 3.1.3.78) with the following enzymatic properties:
The enzyme does not hydrolyze other phosphoinositides including:
This substrate specificity positions TMEM55A as a specific regulator of the PtdIns-4,5-P2 pool at lysosomal membranes.
TMEM55A is predominantly localized to lysosomal membranes where it regulates:
TMEM55A is implicated in Parkinson's disease pathogenesis through its involvement in the endolysosomal pathway—a cellular system critical for protein degradation, membrane recycling, and autophagy. The endolysosomal pathway is one of several key cellular systems dysregulated in PD, alongside mitochondrial dysfunction, neuroinflammation, and protein aggregation.
Key findings from PMID:41866087:
TMEM55A participates in phosphatidylinositol (PI) metabolism, which regulates:
Dysregulation of PI signaling contributes to alpha-synuclein accumulation, impaired autophagy, and dopaminergic neuron vulnerability—all hallmarks of PD pathogenesis.
TMEM55A represents a promising therapeutic target because:
TMEM55A (PIP4P2) is closely related to TMEM55B (PIP4P1) on chromosome 14q11.2:
| Feature | TMEM55A (PIP4P2) | TMEM55B (PIP4P1) |
|---|---|---|
| Gene ID | 55529 | 90809 |
| Chromosome | 8q13.1 | 14q11.2 |
| Protein Length | 257 aa | 277 aa |
| UniProt | Q8N4L2 | Q86T03 |
| OMIM | 609864 | 609865 |
Both proteins function as phosphatidylinositol-4,5-bisphosphate 4-phosphatases and are implicated in lysosomal positioning and endolysosomal biology. The 2025 multi-omic study identified both as potential therapeutic targets in PD.