The accentuation on improving the dairy industry has been to concentrate on breeds that have high milk yields, mainly Holstein. Bovine mastitis continues to be the most powerful disease threatening dairy industry worldwide. It remains the major challenge to the overall dairy industry regardless of the far reaching execution of mastitis control strategies. The immune response to mastitis is complex and requires the development of a sophisticated regulatory system to carry out functions at signal-specific and gene-specific levels which, can be used in dairy breeding selection. The aim of this study is to find out whether a three base insertion located at the glycine stretch of forebrain embryonic zinc finger-like (FEZL) gene, a transcription factor which possibly has an immune function, influences the milk somatic cell count (SCC) and mastitis susceptibility in Egyptian dairy cattle. Furthermore, relationships were explored between FEZL gene and its level of expression and semaphorine 5A (SE-MA5A) gene level of expression, an immune gene through which FEZL has its immune function. Both FEZL and SEMA5A have an important antimicrobial role by controlling the neutrophilic migration to the site of mammary gland infection. Blood was collected from the jugular or mammary gland vein of 112 normal and mastitic unrelated Egyptian Holstein-Friesian dairy cattle. Single-strand conformation polymorphism (SSCP) analysis was carried out to detect single nucleotide polymorphism (SNP) in the amplified glycine stretch of FEZL. The expression levels for FEZL and SEMA5A were assessed in milk samples. Our sequencing results proved that cattle carrying FEZL gene with glycine stretch containing 13 glycine residues have higher SCC and are more susceptible to mastitis than 12G FEZL cattle. Moreover, mastitis and high (SCC) were associated with upregulation in the level of expression of both FEZL and SEMA5A genes. In conclusion, utilizing the SNP of FEZL gene before genetic selection for the dairy industry may be useful to control the incidence of mastitis.