The major sperm protein domain (MSP) is an evolutionarily conserved immunoglobulin-like structure with extracellular signaling and intracellular functions. The C. elegans genome encodes numerous proteins containing MSPs, including about 28 isoforms expressed specifically in sperm. vpr-1 encodes a type II endoplasmic reticulum protein with an N-terminal MSP, coiled coil motif, and C-terminal transmembrane domain. This broadly expressed, ancestral form has homologs in most animal species called VAPs. Human VAPB/ALS8 is associated with amyotrophic lateral sclerosis (ALS), a muscle disease caused by motor neuron degeneration. We have shown that the VAP MSP is proteolytically liberated from the transmembrane domain in the cytosol and secreted by an unconventional mechanism. In C. elegans, the secreted MSP interacts with the CLR-1 Lar-like receptor, thereby promoting mitochondrial localization to body wall muscle I-bands (Han et al. 2012 and 2013). Here we show that muscle mitochondrial abnormalities emerge during larval development. In addition to muscle defects, vpr-1 null mutants are sterile, due to arrested gonad development at the L2-L3 stage. Genetic mosaic and cell type specific expression studies suggest that the germ line, nervous system, and intestine are cellular sites of VPR-1 MSP secretion. Using Cas9 genome-editing technology, we show that endogenous CLR-1 is expressed throughout the muscle plasma membrane in larval and adult worms. MSP to CLR-1 signaling is sufficient to remodel muscle mitochondria during the L4 stage and adulthood, concurrent with gamete development. We used the binary Q system to temporally control VPR-1 expression. The results indicate that VPR-1 is specifically required for gonad development in a short time window around late embryogenesis or early L1. In mammals, VAP MSPs are found in blood and cerebrospinal fluid (Tsuda et al. 2008; Deidda et al. 2014). Similarly, our studies in C. elegans are consistent with VPR-1 MSP being secreted into the pseudocoelom. We are also characterizing mouse Vapb mutants, which have muscle mitochondrial abnormalities in fast-twitch skeletal muscle fibers. Taken together, our data support the model that secreted VAP MSP domains coordinate gonad development with energy metabolism in the neuromuscular system. These results have provocative implications for ALS and other motor neuron degeneration diseases, such as spinal muscular atrophy and Kennedy’s disease.