Sat1, also known as spermidine/spermine N1-acetyltransferase 1, is a rate-limiting enzyme in polyamine catabolism. It is critically involved in converting spermidine and spermine back to putrescine. The gene is associated with pathways such as ferroptosis, and its activity impacts multiple biological processes including cell death, metabolism, and tumor suppression [1]. Genetic models, like KO mouse models, are valuable for studying its functions.

In triple-negative breast cancer (TNBC), SAT1 knockdown inhibited cell proliferation and migration in vitro and in vivo. The transcription factor JUN enhanced SAT1 transcriptional activity, and SAT1 in the cytoplasm bound YBX1 to stabilize it, suppressing autophagy via mTOR mRNA stabilization [2]. In childhood-onset systemic lupus erythematosus, two ultra-rare, predicted loss-of-function (LOF) SAT1 variants showed X-linked recessive inheritance. Hemizygous male and homozygous female Sat1 p.Glu92Leufs*6 KI mice spontaneously developed lupus-like symptoms, highlighting the role of dysregulated polyamine catabolism [3].

In conclusion, Sat1 is essential in polyamine metabolism. Model-based research, especially through KO/CKO mouse models, has revealed its significance in diseases like TNBC and childhood-onset systemic lupus erythematosus. Understanding Sat1's functions provides insights into disease mechanisms and potential therapeutic targets.