Lancl1, or Lanthionine synthetase C-like protein 1, is an antioxidant-related protein with multiple functions. It has been implicated in various pathways, such as those related to oxidative stress regulation, and is biologically important in multiple tissues. Genetic models, especially knockout (KO) mouse models, can help uncover its specific functions [1].

In a transgenic SOD1G93A mouse model of amyotrophic lateral sclerosis (ALS), CNS-specific expression of Lancl1 transgene extended lifespan, delayed disease onset, decelerated symptomatic progression, and improved motor performance. Conversely, CNS-specific deletion of Lancl1 led to neurodegenerative phenotypes, including motor neuron loss, neuroinflammation, and oxidative damage. This indicates Lancl1 is a positive regulator of AKT activity, regulating neuronal survival [1].

In an in vitro model of ischemia mimicked by oxygen and glucose deprivation (OGD) in neuronal HT22 cells, overexpression of Lancl1 by lentivirus transfection preserved cell viability, reduced lactate dehydrogenase release, and attenuated apoptosis. Lancl1 protected against OGD through activating the Akt-PGC-1α-Sirt3 pathway [2].

In prostate cancer cells, suppression of Lancl1 by siRNA increased cancer cell apoptosis, suggesting Lancl1 promotes cell proliferation and protects cells from oxidative stress via suppression of the JNK pathway [3].

In conclusion, Lancl1 plays essential roles in protecting neurons from oxidative stress-related injuries and in the regulation of cell survival in neurodegenerative diseases like ALS and in cancer. The use of KO and transgenic mouse models, as well as in vitro models, has been crucial in revealing these functions, providing potential therapeutic targets for these disease areas.