LAPTM5 (lysosomal protein transmembrane 5) is a lysosomal transmembrane protein preferentially expressed in hematopoietic cells that regulates multiple cellular processes through protein trafficking and lysosomal function 1. The protein contains five transmembrane domains, three PY motifs, and one UIM domain that mediate protein sorting from Golgi to lysosomes and regulate lysosomal stability 1. LAPTM5 functions as a key regulator of immune cell homeostasis by controlling B cell tolerance through BCR internalization and targeting WWP2 for lysosomal degradation, leading to PTEN accumulation and subsequent AKT pathway suppression that triggers apoptosis of autoreactive immature B cells 2. In cancer, LAPTM5 promotes lung-specific metastasis by recruiting WWP2 to mediate BMPR1A lysosomal degradation, blocking BMP signaling and maintaining cancer stem cell traits 3. The protein also serves as an HIV-1 restriction factor in macrophages by transporting viral envelope proteins to lysosomes for degradation, which is counteracted by HIV-1 Vpr 4. Additionally, LAPTM5 expression is transcriptionally regulated by TFEB and contributes to autophagy processes 5. Clinical significance includes its role in drug resistance mechanisms in hepatocellular carcinoma 6 and as a potential biomarker for Alzheimer's disease risk through microglial gene networks 7.