The Rab5 GEF RIN2 and Rab5 GAP RN-Tre/USP6NL are respectively located in nascent and focal adhesions. Due to their enzymatic antagonistic activity on Rab5 GTP-loading and active α5β1 integrin internalization, RIN2 and RN-Tre might co-operate to foster the evolution of nascent into focal adhesions. Moving along stress fibers, active α5β1 integrins generate fibrillar adhesions and FN fibrils, which are not influenced by Rab5. Indeed, in ECs active α5β1 integrin endocytosis at fibrillar adhesions and FN fibril turnover are promoted instead by Rab21.