This study examined changes in LRP130 gene and protein expression in response to an acute bout of sprint‐interval training (SIT) and 6 weeks of SIT in human skeletal muscle. In addition, we investigated the relationships between changes in LRP130, SIRT3, and PGC‐1α gene or protein expression. Fourteen recreationally active men (age: 22.0 ± 2.4 years) performed a single bout of SIT (eight, 20‐sec intervals at ~170% of VO
2peak work rate, separated by 10 sec of rest). Muscle biopsies were obtained at rest (PRE) and 3 h post‐exercise. The same participants then underwent a 6 week SIT program with biopsies after 2 (MID) and 6 (POST) weeks of training. In response to an acute bout of SIT, PGC‐1α
mRNA expression increased (284%, P < 0.001); however, LRP130 and SIRT3 remained unchanged. VO
2peak and fiber‐specific SDH activity increased in response to training (P < 0.01). LRP130, SIRT3, and PGC‐1α protein expression were also unaltered following 2 and 6 weeks of SIT. There were no significant correlations between LRP130, SIRT3, or PGC‐1α
mRNA expression in response to acute SIT. However, changes in protein expression of LRP130, SIRT3, and PGC‐1α were positively correlated at several time points with large effect sizes, which suggest that the regulation of these proteins may be coordinated in human skeletal muscle. Future studies should investigate other exercise protocols known to increase PGC‐1α and SIRT3 protein, like longer duration steady‐state exercise, to identify if LRP130 expression can be altered in response to exercise.