This research paper addresses the hypothesis that the peptidoglycan recognition protein 1 (PGLYRP1) gene polymorphism (Tyr76His; dbSNP ID: ss104796364) has an influence on some performance traits and causes of culling in Polish Holstein-Friesian red-white cows. The study involved 134 cows kept on a farm in the south- west of Poland. PGLYRP1 genotypes TT, CT, and CC were detected. It was shown that compared with cows with genotypes CT and TT, the individuals with genotype CC were characterised by higher lifetime yields and higher amounts of lactation milk, fat, and protein. A beneficial effect of genotype CC, compared with genotype TT, was also noted in the case of the lifespan and, consequently, the length of the productive life and the average number of lactations. Diseases of the musculoskeletal system (genotypes CC and TT) and disorders of the reproductive system (genotype CT) were the most common causes of culling. An essential practical observation was the potentially higher susceptibility of cows with genotype CC to mastitis, which resulted in the necessity to cull over one-fifth of the animals in this group. Simultaneously, no cows in this group were culled due to low performance or metabolic, gastrointestinal, and respiratory diseases. Therefore, the PGLYRP1 gene seems to be a promising potential herd health marker; however, to consider it the main gene, it is necessary to extend the investigations to include more individuals and other breeds of dairy cattle