Lman2, also known as lectin, mannose-binding 2, is a cargo receptor involved in the transport and sorting of glycoproteins. It shuttles between the plasma membrane, the Golgi apparatus, and the endoplasmic reticulum, and is involved in the regulation of the MAPK signaling pathway [2,4].

In sepsis patients, high serum Lman2 levels are associated with septic shock and an unfavorable prognosis, as a high serum Lman2 level (>1.28 ng/ml) was a predictor of 28-day mortality [1]. In breast cancer, Lman2 is highly expressed compared to adjacent normal tissues, and its high expression is correlated with worse patient prognosis. Functionally, Lman2 promotes breast cancer cell proliferation, cell cycle progression, invasion, and chemoresistance while preventing apoptosis. It interacts with MAPK9 to activate the MAPK pathway and confer cisplatin resistance, and knockdown of Lman2 improves the sensitivity of drug-resistant breast cancer cells to cisplatin in vivo [2]. Also in HER2-positive breast cancer, Lman2 is overexpressed, and its knockdown suppresses cell proliferation, migration, and invasion. Lman2 interacts with HEATR3, and up-regulation of HEATR3 reverses the repressive role of Lman2 interference in the progression of HER2-positive breast cancer, Akt/ERK/NF-κB signaling, and the inflammatory response [5].

In the nervous system, Lman2 is a candidate regulatory protein that influences redox-dependent modulation of Kv1.2 channels. Co-expression with Lman2 leads to a pronounced gating shift of Kv1.2 activation to depolarized voltages, and overexpression promotes a slow gating mode of Kv1.2 that mimics the functional outcomes of extracellular reducing conditions [3]. Lman2 also competitively modulates KV1.2 gating with Slc7a5, and specific regions between the S1 to S3 segments of the voltage sensing domain of KV1.2 are distinct for either Slc7a5 or Lman2 sensitivity [6].

In Alzheimer's disease patients, the protein expression of Lman2 related to protein processing and N-glycosylation in the endoplasmic reticulum is upregulated in brain capillaries, along with ribosomal proteins [7].

In conclusion, Lman2 plays crucial roles in multiple biological processes and disease conditions. In sepsis, it is related to prognosis prediction; in breast cancer, it promotes tumorigenesis and drug resistance; in the nervous system, it regulates ion channel gating; and in Alzheimer's disease, it may be involved in protein processing changes at the blood-brain barrier. Studies on Lman2, especially through loss-of-function experiments, contribute to understanding disease mechanisms and may provide potential targets for treatment.