biostudies-literatureBeccari MSNOMIS Stiftung (NOMIS Foundation)NIA NIH HHSHHS | NIH | National Institute of Neurological Disorders and Stroke (NINDS)Muscular Dystrophy Association (MDA)HHS | NIH | National Institute on Aging (NIA)NINDS NIH HHSHHS | NIH | National Institute of General Medical Sciences (NIGMS)NIGMS NIH HHSe2502294122https://www.ebi.ac.uk/biostudies/studies/S-EPMC12130871biostudies-literatureUnknown122(21)Stathmin-2 (also known as <i>SCG10</i>) is encoded by the <i>STMN2</i> gene, whose mRNA is one of the most abundantly expressed in human motor neurons. In almost all instances of ALS and other TDP-43 proteinopathies, stathmin-2 encoding mRNAs are cryptically spliced and polyadenylated in motor neurons, a pathogenic consequence of nuclear loss of function of the RNA binding protein TDP-43. While stathmin-2 has been shown to enhance regeneration after axonal injury to axons of cultured motor neurons, here, we show that after crush injury within the adult murine nervous system of wild-type or stathmin-2-null mice, the presence of stathmin-2 reduces axonal and neuromuscular junction degeneration and stimulates reinnervation and functional recovery. Mechanistically, although stathmin-2 has beenProceedings of the National Academy of Sciences of the United States of AmericaStathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin.PMC12130871N/ARF1NS124203R01 NS124203RF1 NS124203R35GM144121T32 GM008666R35 GM144121T32AG066596P30 NS047101T32GM008666T32 AG066596R01 NS112503R01NS112503P30NS047101Kim DHLutz CMCleveland DWMurgia-Bay BLagier-Tourenne CArnold-Garcia OBaughn MWCorbett KDMcAlonis-Downes MArtates JWLeyva-Cazares DFRangel CKBeccari MSLim JLopez-Erauskin JMelamed ZBernal-Buenrostro CNRubio-Lara HIRamirez-Rodriguez AfalseStathmin-2 enhances motor axon regeneration after injury independent of its binding to tubulin.Stathmin-2 (also known as <i>SCG10</i>) is encoded by the <i>STMN2</i> gene, whose mRNA is one of the most abundantly expressed in human motor neurons. In almost all instances of ALS and other TDP-43 proteinopathies, stathmin-2 encoding mRNAs are cryptically spliced and polyadenylated in motor neurons, a pathogenic consequence of nuclear loss of function of the RNA binding protein TDP-43. While stathmin-2 has been shown to enhance regeneration after axonal injury to axons of cultured motor neurons, here, we show that after crush injury within the adult murine nervous system of wild-type or stathmin-2-null mice, the presence of stathmin-2 reduces axonal and neuromuscular junction degeneration and stimulates reinnervation and functional recovery. Mechanistically, although stathmin-2 has been2025-01-01T00:00:00Z2025 May2026-07-15T07:34:23.611Z2026-07-02T03:08:47.842ZS-EPMC121308714039284510.1073/pnas.2502294122