Lamtor5, also known as HBXIP, is a subunit of the Ragulator. It mediates the activation of mechanistic target of rapamycin complex 1 (mTORC1) in response to amino acids. It is also involved in regulating v-ATPase activity, lysosome function, and has implications in multiple biological pathways related to immune responses and cancer progression [1,2,3,4,5]. Genetic models, such as gene knockout mouse models, have been valuable in studying its functions.

In immune-related studies, myeloid Lamtor5-ablated mice developed SLE-like manifestations. Lamtor5 deficiency in macrophages and PBMCs of SLE patients led to impaired lysosomal function, aberrant mTORC1 activation, blunted autolysosomal pathway, and undesirable inflammatory responses. Mechanistically, Lamtor5 associates with ATP6V1A, a v-ATPase subunit, promoting V0/V1 holoenzyme assembly for lysosome acidification, and affects the lysosomal tethering of Rag GTPase and its interaction with mTORC1 [1].

In cancer research, Lamtor5 has been shown to act as an oncoprotein. For example, in liver cancer, it activates GLUT1 via up-regulating NF-κB [2], and mediates CHOP silence through DNA hypermethylation and miR-182/miR-769 to promote cancer growth [3]. In breast cancer, it raises abnormal initiation of O-glycosylation in metastasis by modulating GALNT1 activity [4].

In conclusion, Lamtor5 plays crucial roles in maintaining immune homeostasis and is involved in cancer progression. The study of Lamtor5 using KO/CKO mouse models has provided insights into its functions in SLE and various cancers, highlighting its potential as a therapeutic target for these diseases.