Skeletal homeostasis is orchestrated by appropriate bone formation and bone resorption, which requires properly regulated cell movements. Profilin1 (Pfn1) is an essential actin polymerization regulator and cell movements. Here, to investigate its function in osteoclasts, we analyzed the osteoclast specific Pfn1 conditional-knockout (cKO). The cKO mice were generated by mating Pfn1flox/flox and CatK-Cre Knock-In (KI) mice. Neonatal cKO mice were delivered without any findings of life-threating defects, with normal genetic segregation. However, we found postnatal growth was slightly affected in cKO mice, and later, the skeletal deformity became significant. At 4 weeks, body length was slightly shorter and the craniofacial deformity was detectable at zygomatic arches and nasal bone by plain radiograms. At 8 weeks, three-dimensional micro-CT (3D-mCT) indicated the impaired growth of cranial base. At this stage, lower- and upper-limb long-bones were significantly shorter than that in wild-type littermates. The long-bones represented the Erlenmeyer-flask deformity, with the appearance of metaphyseal osteolytic expansion. Bone mineral density (BMD), as well as trabecular bone volume (BV/TV) and diaphyseal cortical bone thickness (Ct.th) determined by 3D-mCT were significantly decreased in cKO mice. Histologically, increased endosteal osteoclasts at metaphysis were indicated. These findings suggest that Pfn1 has critical roles in osteoclasts recruitment and motility for maintaining the postnatal skeletal homeostasis, and may be related to osteochondro-dysplastic deformities found in several disorders.