Aedes aegypti are vectors of several devastating arboviruses infecting hundreds of millions of people annually. Controlling mosquito populations by regulating their reproduction is important to minimize viral transmission in the absence of effective antiviral therapies or vaccines. Here, we demonstrate that leucine aminopeptidase1 (LAP1), screened from SWATH-MS-based proteomic data of female spermathecae, is a crucial determinant in mosquito population expansion. Mitochondrial defects and aberrant autophagy of sperm in LAP1 mutant males (LAP1-/-), prepared using CRISPR-Cas9 system, resulted in a reduction of reproduction in wild-type females that mated with them. Additionally, we found that the fitness of LAP1-/- males was strong enough to efficiently transmit genetic changes to mosquito populations through a low number of hatchable offspring, making it to be a promising opportunity to suppress mosquito populations using LAP1-/- males. Importantly, we provide a novel target gene for genetic drive, further amplifying the function of LAP1 in reducing mosquito populations.