The autosomal recessive mutation Gly483Glu, occurring spontaneously in the murine protein Herc1, leads to its overexpression in the cerebellum of the tambaleante mouse (tbl). This causes dysregulation of autophagy-mediated death of Purkinje cells (PC) from two months of age, along with dysregulation of the PI3K/AKT/mTOR signalling pathway responsible for proper axonal myelination. Both situations trigger the onset of an ataxic neuromuscular syndrome characterized by motor control impairments. In response to this disturbance, even before PC death occurs, microglia present in the cerebellum can initiate a potent immune response by acquiring a DAM (disease-associate microglia) phenotype with overexpression of Galectin-3 (Gal3).To study the role of microglia in the degenerative process resulting in PC death in the tbl model, the Lgals3 gene was eliminated to suppress Gal3 expression. Once the new murine model was generated, no changes were observed in the number of microglial cells between the tbl and tbl/Gal3KO groups, although a significant improvement in motor coordination via rotarod tests was found in tbl/Gal3KO mice at two months old. Furthermore, PC and their occupied area in the cerebellum were quantified using immunohistochemistry in two-month-old mice, showing that the population of PC was partially recovered when Gal3 expression was abolished in tbl mice. These results indicate that the lack of Gal3 expression in the tbl model delays the loss of motor coordination characteristic of the ataxic tbl model, without observing any changes in the number of microglia.