SPRY1, also known as Sprouty1, is a crucial negative regulator of the Ras/Raf/ERK signaling pathway [2]. It is involved in multiple biological processes and associated with various pathways. For instance, it is related to the AMFR-mediated pathway in pulmonary fibrosis, NF-κB signaling in pancreatic cancer and testicular immune homeostasis, and Hedgehog pathway in acute myeloid leukemia [1,2,3,4].

In pancreatic cancer, SPRY1 knockdown suppressed tumor growth in mice. SPRY1 was found to promote CXCL12 expression and facilitate neutrophil and macrophage infiltration via CXCL12-CXCR4 axis [2]. In acute myeloid leukemia, SPRY1 knockdown inhibited the proliferation and cell cycle progression of K-562 and HL-60 cells, and facilitated apoptosis [3]. In the testes of male mice, knockdown of Dmrt1, which positively regulates Spry1, led to a broad inflammatory response in seminiferous tubules, indicating Spry1's role in maintaining testicular immune homeostasis [4]. In BRAF-mutant cutaneous melanoma, knockout of Spry1 (Spry1KO) led to cell cycle arrest, apoptosis, and reduced tumor growth in vivo, along with impaired HIF1α-dependent glycolysis and angiogenesis [5].

In conclusion, SPRY1 plays diverse and significant roles in multiple biological processes and disease conditions. Gene knockout models, such as Spry1KO in mice, have been instrumental in revealing its functions in cancer, fibrosis, leukemia, and testicular immune regulation. These findings provide potential therapeutic targets for related diseases.