Stathmin-2 (STMN2) is a microtubule-associated protein that promotes microtubule instability and is targeted to vesicles. It is well established that STMN2 is upregulated after injury, however, the biological relevance and the mechanisms activated by a transient increase of STMN2 remain unknown. Using Xenopus tropicalis tadpoles as animal model we observed that STMN2 levels peaked in a population of motoneurons three days after the transection of the spinal cord, before tadpoles recovered their swimming capacity within 5 to 7 days. To investigate the possible role of STMN2 in the process of re-innervation, a transient upregulation of STMN2 was reproduced in vitro by transduction of autaptic neuronal cultures with STMN2-GFP. We observed a significant increase in spontaneous neurotransmitter release but, evoked neurotransmission remained unaffected. Since changes in synaptic transmission could be attributed to the direct effect of STMN2 on microtubule dynamics, we analyzed how vesicles targeted with STMN2-GFP affected microtubule stability. We found an overall impairment of microtubule growth assessed with EB3-tdtomato in the vicinity of vesicles tethered to STMN2-GFP. Altogether, these results suggest that neurons must increase STMN2 levels to successfully re-establish connectivity. The mechanism could involve an enhancement of microtubule instability driving to an increase of spontaneous neurotransmitter release. This possibility is sustained by a previous study (Velasco et al., 2023). Considering the fundamental role of spontaneous neurotransmitter release in the assembly of neuronal circuits, we suggest a link between STMN2, microtubule dynamics and, spontaneous neurotransmitter release to promote the formation of new synaptic contacts.