Overexpression of sarcolipin (SLN), a regulator of sarco(endo)plasmic reticulum Ca²⁺-ATPases (SERCAs), stimulates calcineurin signaling to enhance skeletal muscle oxidative capacity. Some studies have shown that calcineurin may also control skeletal muscle mass and remodeling in response to functional overload and unload stimuli by increasing myofiber size and the proportion of slow fibers. To examine whether SLN might mediate these adaptive responses we performed soleus and gastrocnemius tenotomy in wild-type (WT) and Sln¬-null (Sln^-/-) mice and examined the overloaded plantaris and unloaded/tenotomized soleus muscles. In the WT overloaded plantaris, we observed ectopic expression of SLN, myofiber hypertrophy, increased fiber number, and a fast-to-slow fiber type shift, which were associated with increased calcineurin signalling (NFAT dephosphorylation and increased stabilin-2 protein content) and reduced SERCA activity. In the WT tenotomized soleus, we observed a 14-fold increase in SLN protein, myofiber atrophy, decreased fiber number, and a slow-to-fast fiber type shift, which were also associated with increased calcineurin signalling and reduced SERCA activity. Genetic deletion of Sln altered these physiological outcomes, with the overloaded plantaris myofibers failing to hypertrophy, increase in fiber number, and transition towards the slow fiber type, while the unloaded soleus muscles exhibited greater myofiber atrophy, reductions in fiber number, and an accelerated slow-to-fast fiber type shift. In both the Sln^-/- overloaded and unloaded muscles, these findings were associated with elevated SERCA activity and blunted calcineurin signaling. Thus, SLN plays an important role in adaptive muscle remodeling potentially through calcineurin stimulation, which could have important implications for other muscle diseases and conditions.