Bishop Natale Paganelli was born on 24th December 1956 in Grignano, a town of Bergamo, Italy. His late parents were Egidio and Maria Paganelli (nee Pagnoncelli) . Natale was the second-to-last of their six sons. He was baptized on Christmas Day 1956, received first communion in 1965 and was confirmed by Bishop Clemente Gaddi in 1967.

Natale started primary school in his own town in 1962. During those years it was customary for missionaries to visit the schools and it was in one of these encounters that the young pupil responded favourably to a question posed by a visiting missionary: "Who would like to become a missionary?" Meanwhile he continued serving at Mass and praying the Rosary with the family at home.

On 29th September 1967 he joined the Xaverian Junior Seminary. Later he did a Teachers’ Course. He then went to the noviciate, and after a period of reflexion and prayer, he decided to consecrate his life to God in the Xaverian Missionary Congregation. On 31st August 1975, he took the First Vows. It was during the novitiate that he lost his father.

After the Noviciate, he studied Philosophy and Theology in the Xaverian Seminary at the Mother House in Parma. During his second year of theology, he took the final decision to consecrate his life to God as a Xaverian Missionary. On 3rd December 1979, he took the Final Vows and on 8th December 1979 he was ordained deacon. After one year, he was ordained priest on 26th December 1980 by Bishop Amilcare Pasini, Bishop of Parma, in the Chapel of the Xaverian Mother House, where the Founder of the Xaverian Missionaries, St. Guido Maria Conforti, is buried.

He obtained the Bachelor in Theology in 1981, and was assigned to México, where he spent 22 years of his missionary life. He served as Vocation Director, Bursar, Rector of the Junior Seminary, Vice Novice Master, Rector of the Philosophy Course, Regional Superior (1996-2002). In 2003 he was assigned to Sierra Leone.

Before coming to his new assignment went to London to study English. During this time he lost his mother.

Bishop Natale arrived in Sierra Leone on 15th August 2005 and was first assigned to Our Lady of Grace Parish, Madina, Tonko Limba, as assistant parish priest; then in 2007 to Lungi Town. In December 2007, he was elected Regional Superior of the Xaverian Missionaries in Sierra Leone, until 11th April 2012 when the Holy Father, Benedict XVI, appointed him Apostolic Administrator of the Diocese of Makeni.

On 18th July 2015, Pope Francis confirmed him Apostolic Administrator of the Diocese of Makeni and at the same time appointed him titular Bishop of Gadiaufala.