Mutations of the ZP genes affect the zona structure; homozygous frameshift or compound heterozygous variants affecting ZP1 result in mutant ZP1 that sequesters ZP3 during zona biogenesis [159, 160] or prevent the establishment of filament crosslinking in the matrix, which typically preserves the structural stability of the zona, leading to zona absence and infertility [161–163]. Here, ZP1 is linked to Infertility.