I read with great interest the article by Xu et al., recently published in Kidney International. This study reported that Semaphorin 4A (Sema4A) systemic delivery could help recruit neuropilin-1 (Nrp1)–positive regulatory T cells to the kidney and alleviate ischemia-reperfusion injury (IRI). These encouraging results need to be reconciled with previous studies by Xia et al.,who investigated the respective contribution to IRI of semaphorins and their receptor plexins. These authors did not find changes in either kidney function or kidney damage in plexinB2-deficient mice 48 hours after IRI. Furthermore, they could not detect kidney defects in Sema4A-, Sema4B-, Sema4C-, Sema4D-, and Sema4G-deficient mice 7 days after injury. Solely the analysis of triple-knockout mice lacking Sema4B/Sema4D/Sema4G uncovered a role for the class 4 semaphorin family in kidney repair. Although this work emphasized the level of redundancy among these proteins, it also undermined the potential role played by Sema4A alone in the development of IRI.