Lipocalins play a role in the cellular trafficking of pheromones Background: and are involved in allergic responses to domestic pets. However, the cross-reactivity among allergens of this group has been poorly explored, and the pheromone linking capacity is not well characterized. The aim of this study was to explore cross-reactive epitopes and pheromone linking capacity among Rat n 1 and homologues in domestic pets through an in approach. silico ElliPro and BepiPred tools were used to predict B cell Methods:in silico linear and cross-reactive epitopes. The pheromone linking capacity was explored by docking virtual screening with 2-ethylhexanol, 2,5-dimethylpyrazine, 2-sec-butyl-4,5-dihydrothiazole, and 2-heptanone ligands.According to the analysis, Rat n 1 shares 52% identity with Equ c Results: 1, Can f 6, Fel d 4, and Mus m 1 allergens. The overlapping structures analysis revealed high structural homology (root mean square deviation < 1). Four lineal and three discontinuous epitopes were predicted on Ra t n 1. A lineal epitope located between amino acids residues 24 and 36 was highly conserved on all allergens explored. A cross-reactive discontinuous epitope (T142, K143, D144, L145, S146, S147, D148, K152, L170, T171, T173, D174) was also found. Docking molecular simulations revealed the region involved in linking ligands, and we identified the properties of the binding of four pheromones and the binding potential of Rat n 1. Critical residues for interactions are reported in this study.We identified some possible allergens from Conclusions:Rattus , and those allergens could have cross-reactivity with allergens norvegicus from some animals. The results need to be confirmed with studies in vitro and could be utilized to contribute to immunotherapy and reduce allergic diseases related to lipocalins. Minor changes throughout, and new references to upgrade the discussion were added. Any further responses from the reviewers can be found at the end of the article REVISED PubMed Abstract | Publisher Full Text 2. Konradsen JR, Fujisawa T, van Hage M, et al.: Allergy to furry animals: New insights, diagnostic approaches, and challenges. J Allergy Clin Immunol. 2015; 135(3): 616-25. PubMed Abstract | Publisher Full Text 3. Sánchez A, Cardona R, Sánchez J: Análisis in silico de lipocalinas de perro, gato, caballo, vaca, hámster y gallina. Posible efecto en el estudio de las enfermedades alérgicas. Revista Alergia México. 2016; 63(1): 1-10. Publisher Full Text 4. Gergen PJ, Mitchell HE, Calatroni A, et al.: Sensitization and Exposure to Pets: The Effect on Asthma Morbidity in the US Population. J Allergy Clin Immunol Pract. 2018; 6(1): 101-107 e2. PubMed Abstract | Publisher Full Text | Free Full Text 5. Liccardi G, Salzillo A, Sofia M, et al.: Sensitization to rodents (mouse/rat) in an urban atopic population without occupational exposure living in Naples, Italy. Eur Ann Allergy Clin Immunol. 2012; 44(5): 200-4. PubMed Abstract 6. Fishbein AB, Lee TA, Cai M, et al.: Sensitization to mouse and cockroach allergens and asth...