According to the National Park Service, biologists were alerted of the collision by the Agoura Animal Shelter around 9:30 a.m.
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P-54 was killed on Las Virgenes Road between Piuma Road and Mulholland Highway.
This is reportedly not far from where her mother was hit and killed by a vehicle in January 2018.
Authorities said the mountain lion will be taken to the California Animal Health and Food Safety Lab in San Bernardino for a full necropsy.
P-54 is the 29th mountain lion - and the 10th radio-collared cat - to be killed by a driver in the area since 2002, the National Park Service said in a tweet.
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In April, P-54's baby, P-97, was also hit and killed by a car along the southbound lanes of the 405 near the Getty Center.
He was 18 months old and had recently dispersed from mom, said officials.