Specifically, K345 lactylation of the E3 ubiquitin ligase TRIM21 attenuates ubiquitin-proteasome pathway-mediated STAT1 degradation in macrophages by preventing its interaction with STAT1.<h4>Discussion</h4>This study provides the first evidence that non-histone lactylation (TRIM21 K345) exacerbates inflammatory orchitis and highlights TRIM21 lactylation or CXCL9/10 as promising therapeutic targets for infection-associated male infertility. Here, STAT1 is linked to male infertility.