Mammalian sex chromosomes are enriched for large, nearly-identical, palindromic sequences harboring genes expressed predominately in testicular germ cells. Discerning if individual palindrome-associated gene families are essential for male reproduction is difficult due to challenges in disrupting all copies within a gene family. Here we generate precise, independent, deletions to assess the reproductive roles of two X-linked palindromic gene families with spermatid-predominant expression, 4930567H17Rik or Mageb5. Via sequence comparisons, we find mouse 4930567H17Rik and Mageb5 have human orthologs, 4930567H17Rik is rapidly diverging in rodents and primates, and 4930567H17Rik is harbored in a palindrome in humans and mice, while Mageb5 is not. Mice lacking either 4930567H17Rik or Mageb5 gene families do not have detectable defects in male fertility, fecundity, spermatogenesis, or in gene regulation, but do show differences in sperm head morphology, suggesting a potential role in sperm function. We conclude that while all palindrome-associated gene families are not essential for male fertility, large palindromes influence the evolution of their associated gene families.Summary sentenceMice lacking X-palindromic gene families display normal male fertility, fecundity, spermatogenesis, and gene expression but exhibit differences in sperm head morphology, suggesting a potential role for these gene families in sperm development.